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| 2. |
- Bettegowda, Chetan, et al.
(författare)
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Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
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Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Alström, Per, et al.
(författare)
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Discovery of a relict lineage and monotypic family of passerine birds.
- 2014
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Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of one of the most comprehensive datasets to date of the largest passerine bird clade, Passerida, identified 10 primary well-supported lineages corresponding to Sylvioidea, Muscicapoidea, Certhioidea, Passeroidea, the ‘bombycillids’ (here proposed to be recognized as Bombycilloidea), Paridae/Remizidae (proposed to be recognized as Paroidea), Stenostiridae, Hyliotidae, Regulidae (proposed to be recognized as Reguloidea) and spotted wren-babbler Spelaeornis formosus. The latter was found on a single branch in a strongly supported clade with Muscicapoidea, Certhioidea and Bombycilloidea, although the relationships among these were unresolved. We conclude that the spotted wren-babbler represents a relict basal lineage within Passerida with no close extant relatives, and we support the already used name Elachura formosa and propose the new family name Elachuridae for this single species.
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| 5. |
- Barkowsky, M., et al.
(författare)
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Subjective quality assessment of error concealment strategies for 3DTV in the presence of asymmetric transmission errors
- 2010
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Ingår i: Proceedings of 2010 IEEE 18th International Packet Video Workshop (PV. - 9781424495207 ; , s. 193-200
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Konferensbidrag (refereegranskat)abstract
- The transmission of 3DTV sequences over packet based networks may result in degradations of the video quality due to packet loss. In the conventional 2D case, several different strategies are known for extrapolating the missing information and thus concealing the error. In 3D however, the residual error after concealment of one view might leads to binocular rivalry with the correctly received second view. In this paper, three simple alternatives are presented: frame freezing, a reduced playback speed, and displaying only a single view for both eyes, thus effectively switching to 2D presentation. In a subjective experiment the performance in terms of quality of experience of the three methods is evaluated for different packet loss scenarios. Error-free encoded videos at different bit rates have been included as anchor conditions. The subjective experiment method contains special precautions for measuring the Quality of Experience (QoE) for 3D content and also contains an indicator for visual discomfort. The results indicate that switching to 2D is currently the best choice but difficulties with visual discomfort should be expected even for this method.
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| 6. |
- Cugnet-Anceau, Christine, et al.
(författare)
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A controlled study of consumption of beta-glucan-enriched soups for 2 months by type 2 diabetic free-living subjects
- 2010
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 103:3, s. 422-428
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is associated with a higher cardiovascular risk and there has been a growing interest in using dietary intervention to improve lipid profile and glucose control. The present work aims at analysing the effects of the enrichment of a normal diet with beta-glucan (3-5 g/d) in free-living type 2 diabetic subjects for 2 months, using a palatable soup. This trial was a parallel, placebo-controlled, double-blinded randomised study performed in fifty-three type 2 diabetic subjects. During a 3-week run-in period, subjects daily consumed a ready meal control soup (without beta-glucan). For the following 8 weeks, Subjects were randomly assigned to consume daily either a control soup or a beta-glucan soup. Changes in lipid profile (total cholesterol (TC), HDL- and LDL-cholesterol (HDLc and LDLc), apo B and TAG) and in glucose control (HbA1c and fasting glucose) were measured. There was no significant alteration in lipid profile in the two groups (TC, HDLc. LDLc and apo B). TAG decreased significantly in the beta-glucan group compared with the control group (-0.12 (SD 0.38) v. 0.12 (SD 0.44)mmol/l, P=0.03). HbA1c and fasting glucose were not reduced in any group. A single daily ingestion of 3-5 g beta-glucan, as required by official dietary recommendations for 8 weeks did not change the lipid profile and HbA1c in type 2 diabetic subjects. To improve the metabolic profile of type 2 diabetic subjects in the long term, the quantity, the food vectors and the tolerability of P-glucan products may be re-evaluated.
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| 7. |
- Fensholt, Rasmus, et al.
(författare)
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Greenness in semi-arid areas across the globe 1981-2007 - an Earth Observing Satellite based analysis of trends and drivers
- 2012
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Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257. ; 121, s. 144-158
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Tidskriftsartikel (refereegranskat)abstract
- Semi-arid areas, defined as those areas of the world where water is an important limitation for plant growth, have become the subject of increased interest due to the impacts of current global changes and sustainability of human lifestyles. While many ground-based reports of declining vegetation productivity have been published over the last decades, a number of recent publications have shown a nuanced and, for some regions, positive picture. With this background, the paper provides an analysis of trends in vegetation greenness of semi-arid areas using AVHRR GIMMS from 1981 to 2007. The vegetation index dataset is used as a proxy for vegetation productivity and trends are analyzed for characterization of changes in semi-arid vegetation greenness. Calculated vegetation trends are analyzed with gridded data on potential climatic constraints to plant growth to explore possible causes of the observed changes. An analysis of changes in the seasonal variation of vegetation greenness and climatic drivers is conducted for selected regions to further understand the causes of observed inter-annual vegetation changes in semi-arid areas across the globe. It is concluded that semi-arid areas, across the globe, on average experience an increase in greenness (0.015 NDVI units over the period of analysis). Further it is observed that increases in greenness are found both in semi-arid areas where precipitation is the dominating limiting factor for plant production (0.019 NDVI units) and in semi-arid areas where air temperature is the primarily growth constraint (0.013 NDVI units). Finally, in the analysis of changes in the intra-annual variation of greenness it is found that seemingly similar increases in greenness over the study period may have widely different explanations. This implies that current generalizations, claiming that land degradation is ongoing in semi-arid areas worldwide, are not supported by the satellite based analysis of vegetation greenness. (c) 2012 Elsevier Inc. All rights reserved.
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| 8. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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